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What Are the Clinical Symptoms Associated with Friedreich Ataxia?

Patient Presentation
A 12-year-old female came to clinic for her health supervision visit. She complained of new onset intoeing that had been occurring for more than 6 months. She had not seen a physician for more than 2 years and the family could provide few details about the history. She said that she was more “clumsy” over time and would trip and occasionally fall even when walking on even ground. She denied any pain, numbness, tingling, difficulty with walking distances or up stairs, or fine motor problems including writing, tieing shoes, brushing teeth or eating. She denied any visual problems. They weren’t sure if it was getting worse but the intoeing was obvious to other people. She denied any trauma or infectious diseases other than a cold. The travel and animal contact history was negative and she denied any anxiety or depressive symptoms. Her grades at school were the same and she had the same several friends. The family was moving to another state soon.

The past medical history showed her to be underimmuized, but she was fully immunized for varicella. The family history was negative for any neurological or orthopaedic problems including no intoeing or outtoeing as a younger child. The review of systems showed no fevers, nausea, emesis, changes in hair or skin, or dysuria.

The pertinent physical exam showed a well-appearing female with normal vital signs and growth parameters around the 50th percentile. HEENT showed pupils to be equal, round and reactive to light and accommodation and no nystagmus. Visual acuity was 20/30 bilaterally. Thyroid was normal size without masses. Lungs, heart, and abdomen were normal. She was Tanner 2 for breast. Her skin had a few open comedomes on her checks and nose. Neurologically her cranial nerves were intact. Her strength was normal in upper and lower extremities. She had +1/+2 deep tendon reflexes in the lower extremities and had positive Babinski reflexes. There was no clonus. Sensation and position sense were equivocal in the lower extremities because the patient didn’t seem to fully understand the questioning. She did not appear to have a direct sensory level though. She had normal deep tendon reflexes in the upper extremities. She appeared to have normal rapid alternating movements, but had some past pointing with finger-to-nose testing. She had had a positive Rhomberg test, but negative Gower maneuver. When walking she had intoeing bilaterally and a wider-based gait.

The diagnosis of a chronic, possibly progressive, neurological condition affecting mainly the lower extremities was made. The differential diagnoses included infection (which seemed unlikely), tumor affecting the spinal cord or cerebellum, or a underlying hereditary disease including ataxias. The patient’s clinical course showed that she was referred to a pediatric neurologist who felt her clinical examination was most consistent with a hereditary ataxia, most likely Friedreich ataxia. The family wanted minimal testing, so genetic testing was sent and was positive for Friedreich ataxia. The family moved to another state soon after the diagnosis.

Friedreich ataxia (FRDA) was first extensively described in a series of papers from 1863-1877 by Nikolaus Friedreich at the University of Heidelberg, Germany. In 1996 the genetic mutation was described. It is an autosomal recessively inherited, homologous expansion of the GAA repeat in intron 1 of the frataxin gene on chromosome 9q13. It causes a transcription error leading to a decrease in frataxin which is a mitochondrial protein involved in iron metabolism and other cell functions. Frataxin is seen mainly in the central and peripheral nervous systems, heart, pancreas and skeleton. Frataxin is produced but in decreased amounts, and lack of frataxin causes in-utero lethality of the embryo.

FRDA is the most common cause of autosomal recessive ataxia. Point estimates are up to prevalence 3/100,000 and it is estimated that ~9000 patients in the United States with FRDA at any given time. Age of onset is in early teens with a mean of ~15 years with most cases developing by 25 years, although genetic testing has allowed more adult patients to be identified. FRDA is unfortunately progressive and patients’ have a decreased lifespan at 40 years (+/- 20 years). There is a correlation with the number of repeats with an increased number having increased disease severity. There is no generational anticipation where subsequent generations have increased severity or onset at earlier ages.

Unfortunately, FRDA is progressive and many treatments help to support the patients and decrease side effects to help with mobility and nursing care. Potential treatments being used include antioxidants, frataxin-inducing agents and gene therapy.

Learning Point
Patients with FRDA can have several presentations including neurological problems, scoliosis or pes planus, or sometimes cardiomyopathy. Neurological symptoms usually associated with FRDA include gait and limb ataxia, decreased tendon reflexes, positive Babinski reflex, loss of position and vibratory sense and dysarthria. Older individuals may have an atypical presentation with preservation of tendon reflexes or very slow progression.

Clinical symptoms of Friedreich ataxia include:

  • Neurological
    • Gait ataxia
    • Distal extremity
      • Dysmetria
      • Atrophy and/or weakness
      • Loss of vibratory and proprioception
      • Sensory neuropathy – “stocking and glove”
      • Loss of stretch muscle reflexes
      • Babinski sign positive
    • Head and Neck
      • Nystagmus
      • Head titubation
      • Dysarthria
      • Blindness (rare)
      • Diminished speech perception
      • Vestibular dysfunction
  • Heart
    • Cardiomyopathy – usually hypertropic but can be dilated
    • Mural thrombi can occur and cause embolic strokes
  • Skeletal
    • Scoliosis – very common and progressive
    • Pes cavus
  • Endocrine
    • Diabetes mellitus

Questions for Further Discussion
1. What causes ataxia in general? A review can be found here.
2. What causes hereditary ataxia?
3. What causes intoeing or outtoeing in younger age groups? A review can be found here.

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Friedreich Ataxia and Degenerative Nerve Diseases.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Koeppen AH. Friedreich’s ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011 Apr 15;303(1-2):1-12.

Jayadev S, Bird TD. Hereditary ataxias: overview. Genet Med. 2013 Sep;15(9):673-83.

Aranca TV, Jones TM, Shaw JD, Emerging therapies in Friedreich’s ataxia. Neurodegener Dis Manag. 2016;6(1):49-65.

OMIM. Friedreich Ataxia 1; FRDA. Available from the Internet at (rev. 9/13/16, cited 2/6/17).

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Causes Uveitis?

Patient Presentation
A 13-year-old male came to clinic with a 2 day history of blurred vision. He noticed the problem in the evening but thought that it was just because he was tired. The next day it continued and he told his parents that he also had some “black spots” that seemed to move around. He denied pain, photophobia or any visual field cuts or narrowing of the visual fields. His mother said that initially she noticed that his left eye was slightly redder but he had been rubbing it trying to relieve the symptoms. She said that it was now normal after he stopped rubbing the eye. He had been well and denied any eye, head or neck trauma. He had been born in the United States and there was no travel outside the United States nor contact with people who had been visiting overseas. He drank city water and had no animal exposures except for a guinea pig at a friend’s house but he had not touched the animal in several months. The past medical history was positive for a left tibial toddler’s fracture at age 3. The review of systems was negative for fevers, chills, nausea, emesis, diarrhea, dysuria, cough, rhinorrhea, edema, weight loss or gain, skin, hair or nail changes or phonophobia. There was also no arthralgia, myalgia, warmth in any joint or difficulty moving.

The pertinent physical exam showed a well-appearing male with normal vital signs and growth parameters around the 75%. He had a normal weight curve since his last visit. His visual acuity was 20/50 in his left eye and 20/30 in his right eye. Pupils were equal, round, and reactive to light. Extra ocular movements were intact. His eye examination showed some photophobia. There was no obvious leukocoria or hypopyon noted. Disc margins appeared sharp but vessels were difficult to evaluate because he kept closing his eyes. His HEENT was negative including thyroid masses. His skin, hair and joint examinations were normal. The rest of his examination was normal.

The diagnosis of acute onset of visual changes including decreased acuity and “floaters” with an otherwise negative history and physical examination was made. The pediatrician referred the teenager to pediatric ophthalmology the following day who diagnosed him with par planitis after various ophthalmological testing which showed snowbanks and snowballs in the vitreous bilaterally.

The laboratory evaluation included a chest radiograph, and blood and urine testing for immune diseases and infectious diseases. Quantiferon gold was performed for possible tuberulosis. All testing was eventually negative and the patient was started on oral steroids. The patient was to followup in 1 month with the ophthalmologist, but the pediatrician contacted the family by phone after 2 weeks and the patient said that he had less floaters and blurred vision subjectively.

Inflammation of the middle layer of the eye, or uvea, is termed uveitis. Uveitis can be divided into anterior, intermediate or posterior uveitis by involving the anterior (iris and ciliary body), intermediate (vitreous) or posterior (choroid and usually retina) compartments. Panuveitis involves all 3 compartments. Duration can also be used to classify uveitis. Acute is 6 weeks and > 3 months is chronic persistent uveitis. Episodic periods of inactivity and reactivity that last more than 3 months are called recurrent uveitis. A third way to characterize uveitis is if it is granulomatous or not. Uveitis increases with age with the highest incidence and prevalence in > 65 year olds. Only ~10% of uveitis occurs in the pediatric age group. Uveitis can be difficult to identify in younger children as they cannot as readily communicate their visual problems. Younger children unfortunately seem to have worse long-term outcomes too.

Pars planitis is a non-granulomatous, chronic, intermediate uveitis of unknown cause (subvariation of idiopathic), but felt to be immune-mediated with a linkage to HLA-DR2 and HLA-DR15. It occurs in children and teens and is possibly more common in males but studies disagree. Patients can be asymptomatic or often have an insidious onset of blurred or decreased vision or floaters. Other less common symptoms are pain, redeye or photophobia. Young children can have strabismus or leukocoria. The eyes are often asymmetrically involved but usually there is some uveitis present in both eyes. Pars planitis is characterized by snowball formation or inferior snowbanking in the vitreous. Potential complications of pars planitis include: cataracts, posterior synechiae, cystoid macular edema (most common cause of visual morbidity), optic disc edema, glaucoma, vitreous hemorrhage, retinoschisis or rarely retinal detachment. Despite these potential complications prognosis is usually good.

Treatment of uveitis tries to balance arresting the inflammation with the potential side effects of the medication. Steroids are often used topically, orally or periocularly injected. Immunosuppressive agents such as methotrexate or biological agents such as adalimamab or infliximab have been used. Complications may need surgical intervention. The outcome of uveitis depends on the diagnosis, treatment and complications encountered by an individual patient.

Learning Point
The workup for uveitis includes evaluation for infectious, immune and malignancies etiologies before any treatment is begun and includes many of these entities below.

Causes of uveitis include:

  • Immune
    • *Idiopathic
    • *Juvenile idiopathic arthritis (JIA)
    • Behçet’s disease
    • Blau syndrome
    • Cogan syndrome
    • Inflammatory bowel disease
    • Multiple sclerosis
    • *Pars Planitis
    • Sarcoidosis
    • Sympathetic opthalmia
    • Tubulointerstitial nephritis-uveitis (TINU) syndrome
    • Vogt-Koyanagi-Harada syndrome
  • Infectious
    • *Viral
      • Cytomegalovirus
      • Epstein Barr virus
      • Herpes simplex virus
      • Rubella
      • Varicella
    • Parasitic
      • *Toxoplasma
      • Ascaris
      • Toxocara
    • Bacteria
      • Tuberculosis
      • Bartonella
      • Borrelia burgdorferi
      • Treponema pallidum
  • Mimicks Uveitis
    • Leukemia
    • Retinoblastoma

* In a study of 527 patients in the US, the most common cause for anterior uveitis was JIA, intermediate uveitis was par planitis and posterior uveitis was toxoplasmosis.

Questions for Further Discussion
1. What is the role of a pediatrician with an uveitis patient?
2. Besides opthalmology, what other specialties may have a role in the care of an uveitis patient?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Eye Diseases.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Smith JA, Mackensen F, Sen HN, Epidemiology and course of disease in childhood uveitis. Ophthalmology. 2009 Aug;116(8):1544-51.

Reiff A, Kadayifcilar S, Ozen S. Rheumatic inflammatory eye diseases of childhood. Rheum Dis Clin North Am. 2013 Nov;39(4):801-32.

Ozdal PC, Berker N, Tugal-Tutkun I. Pars Planitis: Epidemiology, Clinical Characteristics, Management and Visual Prognosis. J Ophthalmic Vis Res. 2015 Oct-Dec;10(4):469-80.

Gupta A, Ramanan AV. Uveitis in Children: Diagnosis and Management. Indian J Pediatr. 2016 Jan;83(1):71-7. 2016 Jan;83(1):63-70.

Castiblanco C, Meese H, Foster CS. Treatment of pediatric uveitis with adalimumab: the MERSI experience. J AAPOS. 2016 Apr;20(2):145-7.

Dajee KP, Rossen JL, Bratton ML, Whitson JT, He YG. A 10-year review of pediatric uveitis at a Hispanic-dominated tertiary pediatric ophthalmic clinic. Clin Ophthalmol. 2016 Aug 22;10:1607-12.

Shoughy SS, Kozak I, Tabbara KF. Associations of Systemic Diseases with Intermediate Uveitis. Ophthalmic Epidemiol. 2016;23(1):27-31.

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital

What Is the Mole Alphabet Again?

Patient Presentation
An 8-year-old female came to clinic for her health supervision visit. She and her parents had no concerns about her health or development. The past medical history was non-contributory. The family history was positive for light-skinned individuals with many freckles but no other dermatological problems.

The pertinent physical exam showed a happy female with normal vital signs and growth parameters in the 75-90%. Her physical examination was normal except for many freckles scattered across her nose and cheeks, on her light complected skin. She had one nevus on her upper shoulder that was 4 mm, flat, uniformly medium brown with symmetric borders and no halo of surrounding skin. The diagnosis of a healthy female was made. When the nevus was noted the mother said that it showed up recently. She felt that it didn’t look bad to her and she felt it had not changed in any way. The pediatrician agreed with her assessment and reviewed the ABCDE’s of skin lesions and recommended that especially because of her light complected skin that she use sunscreen daily.


Melanocytic nevi or moles are pigmented nevi that are extremely common in children with ~ 98% of Caucasian children having at least 1 by early childhood. They are caused by benign melanocyte growth. These nevi reside in the epidermis or dermis, whereas regular melanocytes that produce general skin pigmentation reside in the basal layer. Moles are very often uniform – they basically look the same within the individual. The number of moles increases in the first 2-3 decades of life. Teens having 15-25 moles. They can also disappear.

Congenital melanocytic nevi are found in 1-3% of newborns and grow in proportion to the size of the child. They are graded based on the predicted adult size. Estimated lesion size increase from infancy to adult is 1.7x for the head, 3.3 on the legs and 2.8 on all other body areas. Small (< 1.5 cm) and medium size ( 40 cm) have a 5% lifetime risk. Congenital melanocytic nevi also can change over time. “They may begin as flat, evenly pigmented patches or thin plaques and later become more elevated with lighter, darker, or mottled pigmentation and a mammillated, rugose, verrucous, or cerebriform surface.” They can also develop superimposed papules or nodules which may be concerning for melanoma and need evaluation.

Acquired melanocytic nevi start to appear after 6 months of age. Changing of acquired moles is common. “Most new nevi [are] small and flat, and there [is] a general tendency for existing flat nevi to either become elevated or disappear.” In children they tend to become softer also. Location by itself is not necessarily a problem, but sites such as the head, back or genital area can be more difficult to monitor for the patients and families. Spitz nevus is an acquired, benign melanocytic neoplasm that occurs in children. It often is a single papule on the face or lower extremity that is brown, tan, black, pink or red. On dermatoscopy it appears to have a characteristic sunburst pattern. They are benign but can have histopathological features that overlap with melanoma and therefore a dermatologist usually manages this problem.

Melanoma is always a concern with moles that are not uniform in some way. Melanoma is very rare in children before puberty and uncommon in teens. For those < 10 years of age the lifetime risk is ~ 0.05%, and for patients 10-20 years the lifetime risk is ~0.5%. If there is a concern for possible melanoma, then a dermatologist should be consulted for help with initial evaluation and potentially for ongoing monitoring.

Learning Point
The alphabetical mnemonic for possible melanoma when assessing moles is:

A – Asymmetry – when the lesion is bisected, one half of the individual lesion looks different from the other half in size, shape, texture or color.
B – Borders – a mole should have uniformly well-demarcated or crisp edges. Borders that are irregular or ill-defined are suspicious.
C – Color – a mole should have uniform color. Multiple colors or blue, black, white or red areas are cause for concern.
D – Diameter – while moles can be any size, those that are > 6 mm (size of a pencil eraser) are more concerning.
E – Evolution – A mole that is changing in size, shape, texture or color is concerning. Normal moles in children can become softer and elevated slowly over time. If changing quickly or different from the evolution of other moles in an individual patient, this is concerning.
New symptoms such as itching, bleeding or crusting is also a reason for concern.

“Ugly duckling” is the term used for a mole that is very different than other moles in the same patient. An ugly duckling is also a concern. “Melanomas in children tend to be amelanotic and nodular, presenting as a rapidly growing “bump” that may mimic a pyogenic granuloma, keloid or wart rather than a changing nevus.”

Questions for Further Discussion
1. How do you monitor nevi in your practice?
2. What type of sunscreen do you recommend to use and at what age do you recommend starting to use it?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Moles and Melanoma.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Schaffer JV. Pigmented lesions in children: when to worry. Curr Opin Pediatr. 2007 Aug;19(4):430-40.

Schaffer JV. Update on melanocytic nevi in children. Clin Dermatol. 2015 May-Jun;33(3):368-86.

Mann JA. Update on pediatric dermatologic surgery from tots to teens. Curr Opin Pediatr. 2014 Aug;26(4):452-9.

Society for Pediatric Dermatology. Patient Perspectives: Moles and melanoma in children and teens. Pediatr Dermatol. 2015 Nov-Dec;32(6):e320-1.

Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa Children’s Hospital