Alpha-fetoprotein as a biomarker for recessive ataxias

Abstract

Alpha-fetoprotein (AFP) is a fetal protein produced in the yolk sac and in the fetal liver. AFP has been implicated in both ontogenic and oncogenic growth disorders 1 . Although the main biologic role of AFP during pregnancy remains controversial to this day, AFP has been related to fetal birth defects and tumors 1 . AFP is recognized as one of the first tumor markers. It was first associated with hepatocellular carcinomas and later to germ cell tumors 2 . The autosomal recessive ataxias, including ataxia-telangiectasia (AT) and ataxia with oculomotor apraxia type 2 (AOA2), belong to a special group of hereditary ataxias with heterogeneous presentation. Simple laboratory studies, like AFP measurement, have been reported to be helpful in the differential diagnosis of ataxias.The purpose of this review is to describe the association of serum AFP with recessive ataxias. We report the clinical and laboratory findings of three patients with a recessive ataxia profile. CASESWe identified two patients with clinical and laboratory features of AOA2 and one patient with AT. Informed and written consent were obtained from all participants. Patient 1A 28-year-old man was seen at the neurology department with a twelve-year history of progressively worsening balance. He had been a normal full-term delivery from consanguineous parents. His intelligence was normal. Over the years, he developed difficulties in writing and speaking. The symptoms progressed slowly over the following years.His neurological examination showed muscle strength 5/5, with absent reflexes. An ataxic gait with mild enlargement of lower-limb basis, considerable staggering and difficulties with half turn were observed. He was unable to perform tandem walk (heel-to-toe). Finger-nose and heel-shin ataxia were evident. He presented clumsiness of fine finger movements. Gaze-evoked horizontal nystagmus, ocular saccadic overshot, ocular apraxia and cerebellar dysarthria were also present. Vibration and position senses were also impaired. Fundoscopy and visual acuity were normal, and there were no telangiectasia.In order to score the cerebellar dysfunction, we used the International Cooperative Ataxia Rating Scale (ICARS). It consists of four parts: postural and stance disorders (7 items; 34 points), limb ataxia (7 items; 8 points), dysarthria (2 items; 8 points), and oculomotor disorders (3 items; 6 points), with a total of 100 points 3 . The patient reached a score of 47.Specific laboratory studies were as follows: albumin: 4.2 g/dl (3.2-5.6 g/dl); total cholesterol: 200 mg/dl (<200 mg/dl); AFP: 9.2 IU/ml (<5.5 IU/ml); vitamin E: 0.5 mg/ dl (0.5-1.8 mg/dl). Routine blood and urine testing, echocardiogram and electrocardiogram (EKG) were all normal. The audiogram showed normal hearing. A genetic study for Friedreich ataxia was negative.Brain magnetic resonance imaging (MRI) revealed atrophy of the cerebellar hemispheres and vermis, with relative preservation of the brainstem and no ab-

Progressive Ataxia with Elevated Alpha-Fetoprotein: Diagnostic Issues and Review of the Literature

“…2,11 Importantly, AFP elevation is an almost universal feature of AOA2 (present in 99–100%) but it does not correlate with DD or disease severity in AOA2, preventing its use as a disease biomarker. 2,4,8 AFP is still a very useful diagnostic tool for A-T and AOA2, 12,13 although sometimes repeated measurements are required before elevated levels can be established. 2 Other clinical clues favoring AOA2 are the lack of immunodeficiency, pulmonary symptoms, and family history of cancer.…”

Clinical spectrum of early onset cerebellar ataxia with retained tendon reflexes: an autosomal recessive ataxia not to be missed

“…For instance, SYNE1 mutation is a gene responsible for a recessive inherited pure cerebellar ataxia 13 . Concerning that genetic test is not available for the diagnosis of EOCA, we strongly recommend a biomarker investigation, including albumin, alphafetoprotein and vitamin E, and genetic test for FA, in order to exclude other potential ARCA 14 . A B…”