An adolescent with newly diagnosed Wilson disease having underlying type 1 diabetes: A previously unreported combination

ABSTRACT

Wilson’s disease is a copper deposition disease; involving the brain, liver, and eyes with onset commonly in adolescent age group. The onset of symptoms typically occurs around 12–15 years of age. The usual manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). It has been seen associated with various endocrinopathies like hypothyroidism and hypoparathyroidism but its association with type 1 diabetes mellitus very rare. To the best of our knowledge, no case has been reported about association of type 1 diabetes mellitus with Wilson disease. Here we report a case of 14-year-old male patient, who was diagnosed with type 1 diabetes mellitus one year back, now presented with neurological symptoms. On further investigations patient was found to have Wilson’s disease.

Introduction

Wilson’s disease is an autosomal recessive disorder caused by mutation in ATP7B gene on chromosome 13 leading to defect in biliary copper excretion. The incidence is one in 30,000 to one in 50,000 births worldwide. It is associated with degenerative changes in the liver, brain, and eyes. One-third of patients usually presents with neurological symptoms.[1] Unusual manifestations include arthritis, pancreatitis, and various endocrinopathies like hypothyroidism, hypoparathyroidism, hypogonadotropic hypogonadism, and metabolic bone disease.[2]

Type 1 diabetes mellitus is a chronic autoimmune condition due to insulin deficiency leading to hyperglycemia with associated complications. It has been seen with various genetic disorders (e.g., Down’s syndrome, Klinefelter syndrome and Noonan syndrome), autoimmune (e.g., thyroid and adrenal disorders, myasthenia gravis, SLE and rheumatoid arthritis) and central nervous system diseases.[3] Herein, we report a case that has rare combination of Wilson disease with type 1 diabetes.

Case Report

A 14 years old male child presented to our pediatrics emergency department with complaints of abnormal twisting movements of both upper and lower limbs with difficulty in speaking for last 30 days. These movements gradually increased in severity to such an extent that child become non-ambulatory. There were no complaints of fever, convulsions, rash, facial deviation, visual or auditory problems. One year back patient was diagnosed with type 1 diabetes mellitus and he was on regular insulin with poor glycemic control. On admission, his Glasgow coma scale was E4 V5M6 with blood pressure 114/74 mm Hg, pulse rate 78/min, respiratory rate 18/min with normal oxygen saturation and no apparent respiratory distress. His cranial nerves were intact. He had no focal deficit, sensory disturbances, ataxia, or meningeal sign. Motor examination revealed increased tone of all limbs, power 5/5 in all limbs with normal deep tendon reflexes and flexor plantar response. Ophthalmologic examination reveals Kayser- Fleischer rings in both eyes, confirmed on slit lamp examination [Figure 1]. Laboratory investigations revealed Hb 10 gm/dl, total leukocyte count of 14,600/mm³, blood sugar 686 mg/dL, HbA1c 12.14%, sodium levels of 134 mEq/L with glycosuria with no ketonuria. Levels of vitamin D3, serum and ionized calcium were normal. Liver function tests showed SGPT 460 U/l and SGOT 600 U/l. USG abdomen showed altered echotexture of liver measuring 14 cm. Serum ceruloplasmin levels were 10 mg/dl with increased 24-hour’s urinary copper levels (155 ug/d). MRI brain was planned which showed T2 and FLAIR hyperintensities in bilateral basal ganglia, lateral part of thalami with subtle similar signals in midbrain, posterior part of pons (including periaqueductal region) with mild cerebral atrophy with prominence of lateral ventricles [Figure 2]. Based on the laboratory and radiological findings, diagnosis of Wilson’s disease was made. Patient was started on diabetic diet and lispro-glargine insulin regimen. Chelation therapy with d-penillamine at 20 mg/kg/day and zinc (25 mg thrice daily) was started. Patient had significant improvement in abnormal movements and speech after 2 weeks of therapy with good glycemic control. The patient was discharged and is currently in our follow-up. Parents’ consent was obtained for publication purpose as patient is minor.

Figure 1.

Slit lamp examination showing Kayser Fleischer ring in cornea

Figure 2.

MRI brain showed T2 and FLAIR hyperintensities in bilateral basal ganglia, lateral part of thalami with subtle similar signals in midbrain, posterior part of pons with mild cerebral atrophy with prominence of lateral ventricles

Discussion

Wilson’s disease is a genetic disorder characterized by impaired copper metabolism, stemming from mutation that disrupt copper metabolism, causing diminished biliary copper excretion and diffuse copper accumulation within hepatocytes.[1] With time liver cells become overloaded and copper is deposited in other tissues, mainly brain, eyes, and kidneys, causing toxicity. Clinical features of WD include hepatic (asymptomatic hepatosplenomegaly hepatitis, cirrhosis, and liver failure), neurological (dystonia, choreoathetoid movements) and neuropsychiatric manifestations. KF ring is seen in more than 90% of patients with neurological manifestations. Our patient presented with dystonic movements with dysarthria. Our patient also had KF ring confirmed by slit lamp examination. Most frequently affected sites of the brain are bilateral basal ganglia followed by midbrain, pons, and thalamus.[4] MRI brain of index case also showed typical findings of WD. Although Wilson’s disease has been reported with various autoimmune diseases but its coexistence with type 1 diabetes mellitus has not been reported in the literature.

Li et al.,[5] reported a case of a 47-year-old man, who presented with uncontrolled high blood glucose and abnormally elevated hepatic transaminases. Laboratory investigations revealed decreased ceruloplasmin and elevated 24 hour urinary copper levels with HbA1c levels of 14%. MRI brain showed typical findings of WD. Sequencing of ATP7b gene revealed one heterozygous mutation (c.525 dupA) in exon 2 and one heterozygous mutation (c.2930 C>T) in 13, which were known to pathogenic mutations. In our case genetic analysis could not be done due to financial constraints.

Our proposed mechanism suggests that the concomitant presence of WD and diabetes involves the dysregulation of the Fas/FasL system, which has been implicated in the pathogenesis of various autoimmune disease, potentially contributing to the complex interplay between these two conditions.[6]

However, more case studies are required to conclude a causal association between these two entities.

Conclusion

This case report highlights, although very rare, the coexistence of Wilson’s disease and type 1 diabetes mellitus. So, any patient with type 1 diabetes mellitus presenting with neurological or neuropsychiatric symptoms, one should always suspect Wilson’s disease and investigate accordingly.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.