Dr. Roach: Course of rare Van der Knaap disease is unclear

Dear Dr. Roach: I have a question that I hope you can help me with. My 1-year-old grandniece (my brother’s granddaughter) was recently diagnosed with Van der Knaap disease after suffering seizures and getting an MRI. An internet search described it as a rare inherited disorder with walking difficulties and a progressive decline in brain function.

I would appreciate any additional information about this disease and its course. I am also concerned about its likelihood of affecting my other relatives. Is there any genetic screening they can get to find out their risks?

— R.K.

Dear R.K.: There are so many rare inherited disorders that it is virtually impossible to know them all. Megalencephalic leukoencephalopathy with subcortical cysts, also called Van der Knapp disease, is most commonly caused by a mutation in one of two separate genes (called MLC1 and HEPACAM). It is passed on as an autosomal recessive disorder, meaning that both parents need to carry a copy of the gene.

Your brother has approximately a 50% chance of being a carrier, and you have a 25% chance of being a carrier. A genetic test can confirm the diagnosis, at which point family members can be screened to see if they carry the gene. A genetic counselor is an essential consultant.

Children with the classic form of the disease usually have large brains and large heads that become more pronounced during the first year of growth. Seizures are common, and the progressive decline in brain function that you mentioned is variable in this condition. But it is generally described as mild. Some of those affected are unable to walk in just a few years, where others continue to walk independently until their 40s at least. There is also an improving form where the affected children do get better over time.

I wish I could give you a better idea of how your grandniece will do, but this is a rare and recently described condition (1995), for which there is no specific treatment. The seizures are treated and generally well-controlled, similar to any other type of epilepsy.

Dear Dr. Roach: I’m a 74-year-old diabetic who had a kidney transplant 22 years ago. I am on glimepiride and metformin. My blood sugar level has been controlled with an average A1C level of 6.3%. About a month ago, I had COVID, and now my blood sugar runs between 160-200 mg/dL. I have read that COVID can affect the insulin production cells in the pancreas. My doctor doubled the glimepiride, with little effect.

My question is, will those cells in the pancreas start working again, or will my doctor have to take a different approach?

— P.L.

Dear P.L.: Resistance to insulin following COVID infections is well-described. While metformin remains an important choice for most people with Type 2 diabetes, glimepiride might not be an ideal choice, since glimepiride works by forcing the pancreas to release more insulin. This effect can fail after years of using this type of medication.

Most experts recommend using insulin in the case of severe insulin resistance, but I suspect that the use of medicines to decrease insulin resistance, such as pioglitazone, might be appropriate.

I recommend a consultation with an expert (an endocrinologist who specializes in diabetes) right away. Diabetes can sometimes be helped by prompt treatment and by keeping the blood sugar in as normal of a range as possible.

Readers may email questions to ToYourGoodHealth@med.cornell.edu.