Clinical, hematological, and imaging observations in a 25-year-old woman with abetalipoproteinemia
A 25-year-old lady presented with a history of progressive nyctalopia since the age of 10 years and impaired hearing since the age of 15 years. The latter was attributed to chronic suppurativeotitis media (CSOM) elsewhere. At the age of 20 years, she developed tremulousness of limbs that was prominent while reaching out for objects as well as with anxiety. This was associated with dysarthria and imbalance of stance and gait that worsened markedly on removing visual cues. There was no history of dystonia, hyperkinetic movement disorders, recurrent infection, malignancies, focal limb deficits, seizures, myoclonus, altered sensorium, psychiatric manifestations, or autonomic system involvement. There was no family history of similar illness.\nShe was born to non-consanguineous parents at term following an uneventful antenatal period. Postnatally, there was failure to thrive with a global delay in the acquisition of all milestones. She suffered from recurrent diarrheal episodes throughout the first decade of life. She was advised a gluten-free diet following a presumptive diagnosis of celiac disease by her pediatrician without any significant respite. Her gastrointestinal symptoms subsided at the age of 10 years. She was also transfused blood on three occasions for severe anemia. She attained menarche at the age of 13 and had normal menstrual cycles.\nOn examination, she was a short-statured (height: 143 cm), thin-built (weight: 31 kg) girl with a very low body mass index (BMI: 15.19 kg/m2), dysmorphic facies in the form of prognathism, hypertelorism, malar hypoplasia, and scoliosis. Fundus examination showed evidence of atypical RP []. She had cerebellar signs in the form of titubation, dysarthria, as well as impaired co-ordination on finger-nose and knee-heel testing. Motor system examination revealed wasting and hypotonia of distal extremities, normal power, and sluggish deep-tendon reflexes. There was a marked impairment of kinaesthetic sensations; bilateral plantar responses were flexor.\nShe had been evaluated elsewhere for malabsorption and anemia. Jejunal biopsy showed only mild focal atrophy; serum tissue transglutaminase (IgA) levels were not elevated (7.05; ref: <15 U/ml: negative). D-xylose excretion was less than normal (0.2 g/5 g; ref: 1 g/5 g), suggesting malabsorption from the small intestine. Peripheral smear done on at least five occasions until the age of 15 years showed varying degrees of anemia (hemoglobin ranging from 3.8 to 8.0 g%), dimorphic red blood corpuscles (RBCs), and poikilocytosis. Examination of bone marrow aspirate showed normoblastic erythropoiesis, with absent marrow iron stores. Stool examination for parasites and occult blood drew negative results. Serum iron (31.08; ref: 35-145 μg/dl) was reduced and total iron binding capacity (TIBC) (558.2; ref: 250-400 μg/dl) was elevated. She received vitamin and iron supplements.\nPresently, at the time of evaluation at our centre, hemogram revealed hemoglobin: 12.4 g%, total leucocyte count (TLC): 5500 cells/mm3, erythrocyte sedimentation rate (ESR): 2 mm (1st h), while the peripheral smear showed normocytic to macrocytic and normochromic RBCs and numerous acanthocytes []. Serum lactate (16.6 mg/dl; ref: 4.5-20 mg/dl), renal and hepatic function tests, serum creatine kinase (CK) (55 U/l; ref: 20-171 U/l), screening for inborn errors of metabolism (IEM) by tandem mass spectroscopy (TMS), thyroid profile (thyroid-stimulating hormone (TSH): 2.45 μU/ml, ref: 0.34-5.0 μU/ml; T3: 140.04 ng/dl, ref: 87-178 ng/dl; T4: 13.4 μg/dl, ref: 6.09-12.23 μg/dl), human immunodeficiency virus (HIV) antibody test, and abdominal ultrasound were within normal limits. Serum ammonia (50.9 μmol/l; ref: 11-35 μmol/l) was mildly elevated. Magnetic resonance imaging (MRI) of brain revealed a normal study; there was no cerebellar atrophy, while the cervical cord showed T2-hyperintense signal changes in the dorsal column []. Routine peripheral nerve conduction studies showed absent sensory nerve action potentials in median, ulnar, and sural nerves with preserved motor conduction parameters. Audiometry showed moderate to severe mixed bilateral hearing loss, suggesting it to be due to combination of conductive (CSOM-related) and sensori-neural (disease-related) deafness.\nThe serum lipid profile was abnormal, with extremely low levels of total cholesterol (34; ref: 110-220 mg/dl), triglycerides (TG) (4; ref: 50-150 mg/dl), high density lipoprotein (HDL) (23; ref: 35-65 mg/dl), very low density lipoprotein (VLDL) (1 mg/dl; ref: 10-40 mg/dl), and low density lipoprotein (LDL) (10; ref: 60-160 mg/dl). Serum apolipoprotein B level was also very low (<20; ref: 60-117 m%). Serum levels of vitamin E (<0.3; ref: 5-18 mg/l) and D (5.24; ref: <10 ng/ml: deficient) were significantly reduced, while B12 (1841; ref: 243-894 pg/ml) and folic acid (12.9; ref: 3-17 ng/ml) were within normal limits.\nBased on the described phenotype, the presence of acanthocytes and low serum cholesterol, TG, HDL, LDL, VLDL, and apolipoprotein B levels, a diagnosis abetalipoproteinemia was considered with secondary vitamin E deficiency. She was initiated on treatment with oral vitamins E (2400 IU/d), D (1000 mg/d), A (400 IU/kg/d), and iron supplementation (ferrous sulphate containing 60 mg of elemental iron/day), and parenteral vitamin K (5 mg/day). There was no follow-up.